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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005781-39 | EudraCT Number |
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| Name | Class |
|---|---|
| Baxalta Innovations GmbH, now part of Shire | INDUSTRY |
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The purpose of this study is to:
15 JUN 2020: The temporary enrollment stop of new patients into this study due to the COVID-19 pandemic has been lifted in one or more countries/sites, and the study is now again enrolling new patients. However, some countries/sites may still have paused the enrollment of new patients due to the pandemic.
23 APRIL 2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1:FEIBA 85±15 U/kg at Regular Volume Then 50% Reduced Volume at 2 U/kg/min Rate or Vice Versa | Experimental | Participants who were eligible were randomized to receive: 3 infusions (infusions 1, 2 and 3) of factor eight inhibitor bypassing activity (FEIBA) 85 ± 15 U/kg, reconstituted in regular volume sterile water for injection (SWFI) followed by 3 infusions (infusions 4, 5 and 6) of FEIBA 85 ± 15 U/kg reconstituted in 50% reduced volume SWFI (Sequence A) or: 3 infusions (infusions 1, 2 and 3) of FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI, followed by 3 infusions of FEIBA 85 ± 15 U/kg, reconstituted in regular volume SWFI (Sequence B). All infusions in Part 1 were given at the standard infusion rate of 2 U/kg/min. |
|
| Part 2:FEIBA 85±15U/kg 50% Reduced Volume at 4U/kg/min Rate Then at 10U/kg/min Rate | Experimental | Participants who completed Part 1, received FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI at an increased rate of 4 U/kg/min for infusions 7, 8, and 9, followed by FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI at an increased rate of 10 U/kg/min for infusions 10, 11, and 12. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FEIBA | Biological | Anti-inhibitor Coagulant Complex Nanofiltered (activated prothrombin complex concentrate [APCC]), FEIBA NF. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Number of Participants With Any Hypersensitivity Reaction | Number of participants with AEs particular to allergic-type hypersensitivity reactions were assessed. Clinical manifestations of hypersensitivity reactions included, but was not limited to skin rash, pruritus (itching), urticaria (hives), angioedema (for example, swelling of the lips and/or tongue) and anaphylactic reaction. | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Number of Participants With Any Thromboembolic Event | Participants with adverse events related to thromboembolic event were reported. Clinical manifestations of thromboembolic events included, but was not limited to myocardial infarction, deep vein thrombosis, pulmonary embolism, stroke and transitory ischemic attack. | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Number of Participants With Any Infusion Site Reaction | Infusion sites were monitored for pain, tenderness, erythema, and swelling. Infusion site evaluations were made by clinical staff or by the participant or caregiver. | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Number of Participants With AEs Leading to Study Discontinuation | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
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Inclusion Criteria:
Greater than or equal to (> or =) 18 to less than or equal to (< or =) 65 years old at the time of screening.
Hemophilia A or B of any severity, with a documented > or = 3 months history of inhibitors (> or = 0.6 Bethesda units [BU]) requiring the use of bypassing agents (FEIBA or rFVIIa) prior to screening. Inhibitor level will be tested at screening if no documented history is available.
Hepatitis C virus (HCV) negative, either by antibody testing or polymerase chain reaction (PCR); or HCV positive with stable liver disease.
Human immune deficiency virus (HIV) negative; or HIV positive with stable disease and CD4 count > or = 200 cells per cubic millimetre (cell/mm3) at screening.
Adequate venous access.
Willing and able to comply with the requirements of the protocol.
If a female of childbearing potential, must have a negative blood pregnancy test and agrees to employ adequate birth control measures for the duration of the study, such as: a. Abstain from sexual intercourse, b. Use a reliable method of contraception (contraception such as an intrauterine device, barrier method [e.g., diaphragm or sponge; female condom not permitted] with spermicide, oral contraceptive, injectable progesterone, sub dermal implant), and have their male partner use a condom
If female of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Shire | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Center Zagreb | Zagreb | 10 000 | Croatia | |||
| PHI Institute for Transfusion Medicine of Macedonia |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants received factor eight inhibitor bypassing activity (FEIBA) reconstituted in regular volume and FEIBA reconstituted in 50% reduced volume in a crossover fashion for Part 1 and FEIBA reconstituted in 50% reduced volume at escalated infusion rates for Part 2. Participants who completed Part 1 entered Part 2 of the study. A total of 45 participants were enrolled in the study out of which 33 participants received the study treatment.
Participants took part in the study at 18 investigative sites in Thailand, Malaysia, Algeria, Croatia, India, Poland, Turkey, and Ukraine from 12 February 2019 to 27 December 2021. Participants with a diagnosis of Congenital Hemophilia A were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Sequence A-FEIBA 85±15U/kg in Regular Volume, Then FEIBA 85± 15U/kg in 50% Reduced Volume | Participants were first randomized to receive 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in regular volume SWFI at the standard rate of 2 U/kg/min, every 48 hours. Participants then received 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in 50% reduced volume SWFI, at the standard rate of 2 U/kg/min, every 48 hours. |
| FG001 | Part 1: Sequence B-FEIBA 85±15 U/kg in 50% Reduced Volume, Then FEIBA 85±15 U/kg in Regular Volume | Participants were first randomized to receive 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in 50% reduced volume SWFI, at the standard rate of 2 U/kg/min, every 48 hours. Participants then received 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in regular volume SWFI at the standard rate of 2 U/kg/min, every 48 hours. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Day 1 up to Day 16 |
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| Part 2: Day 19 up to Day 41 |
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SAS included all participants who received at least one dose of IP (i.e., FEIBA).
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 + Part 2: Overall FEIBA Treatment | Part 1: Participants who were eligible were randomized to receive: 3 infusions (infusions 1, 2 and 3) of FEIBA 85 ± 15 U/kg, reconstituted in regular volume SWFI followed by 3 infusions (infusions 4, 5 and 6) of FEIBA 85 ± 15 U/kg reconstituted in 50% reduced volume SWFI (Sequence A) or: 3 infusions (infusions 1, 2 and 3) of FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI, followed by 3 infusions of FEIBA 85 ± 15 U/kg, reconstituted in regular volume SWFI (Sequence B). All infusions in Part 1 were given at the standard infusion rate of 2 U/kg/min. Part 2: Participants who completed Part 1, received FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI at an increased rate of 4 U/kg/min for infusions 7, 8, and 9, followed by FEIBA 85 ± 15 U/kg, reconstituted in 50% reduced volume SWFI at an increased rate of 10 U/kg/min for infusions 10, 11, and 12. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Any Treatment Emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
At each visit investigator documented occurrence of adverse events(untoward medical occurrence in participant administered IP that does not necessarily have a causal relationship with treatment). SAS=participants receiving at least one dose of IP(FEIBA).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1:FEIBA 85 ± 15 U/kg Regular Volume at 2 U/kg/Min Rate | Participants were randomized to receive 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in regular volume SWFI at the standard rate of 2 U/kg/min, every 48 hours (Participants in Sequence A: infusions 1, 2, and 3 and Participants in Sequence B: infusions 4, 5 and 6). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drug hypersensitivity | Immune system disorders | MedDRA 24.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 7, 2018 | Dec 19, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 19, 2022 | Dec 19, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C065655 | anti-inhibitor coagulant complex |
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|
| Number of Participants With Vital Signs Considered as AEs | Number of participants with vital signs considered as AEs were assessed. Vital signs included body temperature (degree Celsius or degrees Fahrenheit [°C or °F]), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (millimeter of mercury [mmHg]). | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Number of Participants With Laboratory Assessments Considered as AEs | Number of participants with Laboratory Assessments considered as AEs were assessed. Laboratory assessments included hematology, clinical chemistry, coagulation testing, serological testing, pregnancy testing, cluster differentiation 4 (CD4). | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
| Skopje |
| 1000 |
| North Macedonia |
| MV Sklifosovskyi Poltava Hematology | Poltava | 36011 | Ukraine |
| Part 2: FEIBA 85±15U/kg 50% Reduced Volume at 10U/kg/Min Rate | Participants who completed Part 1 of the study and received up to 3 infusions (infusions 7, 8, and 9) at the rate of 4 U/kg/min in Part 2 received up to 3 infusions (10, 11, and 12) of FEIBA 85 ± 15 U/kg IV reconstituted in 50% reduced volume SWFI at an increased infusion rate of 10 U/kg/min, every 48 hours. |
|
| COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Part 1:FEIBA 85±15 U/kg 50% Reduced Volume at 2 U/kg/Min Rate | Participants were randomized to receive 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in 50% reduced volume SWFI, at the standard rate of 2 U/kg/min, every 48 hours (Participants in Sequence A: infusions 4, 5, and 6 and Participants in Sequence B: infusions 1, 2 and 3). |
| OG002 | Part 2:FEIBA 85±15 U/kg 50% Reduced Volume at 4 U/kg/Min Rate | Participants who completed Part 1 of the study received up to 3 infusions of FEIBA 85 ± 15 U/kg IV reconstituted in 50% reduced volume SWFI at an increased rate of 4 U/kg/min, every 48 hours (infusions 7, 8, and 9). |
| OG003 | Part 2:FEIBA 85±15 U/kg 50% Reduced Volume at 10 U/kg/Min Rate | Participants who completed Part 1 of the study and received up to 3 infusions (infusions 7, 8, and 9) at the rate of 4 U/kg/min in Part 2 received up to 3 infusions (10, 11, and 12) of FEIBA 85 ± 15 U/kg IV reconstituted in 50% reduced volume SWFI at an increased infusion rate of 10 U/kg/min, every 48 hours. |
|
|
| Primary | Number of Participants With Any Hypersensitivity Reaction | Number of participants with AEs particular to allergic-type hypersensitivity reactions were assessed. Clinical manifestations of hypersensitivity reactions included, but was not limited to skin rash, pruritus (itching), urticaria (hives), angioedema (for example, swelling of the lips and/or tongue) and anaphylactic reaction. | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| Primary | Number of Participants With Any Thromboembolic Event | Participants with adverse events related to thromboembolic event were reported. Clinical manifestations of thromboembolic events included, but was not limited to myocardial infarction, deep vein thrombosis, pulmonary embolism, stroke and transitory ischemic attack. | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| Primary | Number of Participants With Any Infusion Site Reaction | Infusion sites were monitored for pain, tenderness, erythema, and swelling. Infusion site evaluations were made by clinical staff or by the participant or caregiver. | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| Primary | Number of Participants With AEs Leading to Study Discontinuation | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| Primary | Number of Participants With Vital Signs Considered as AEs | Number of participants with vital signs considered as AEs were assessed. Vital signs included body temperature (degree Celsius or degrees Fahrenheit [°C or °F]), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (millimeter of mercury [mmHg]). | SAS included all participants who received at least one dose of IP (i.e., FEIBA). | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| Primary | Number of Participants With Laboratory Assessments Considered as AEs | Number of participants with Laboratory Assessments considered as AEs were assessed. Laboratory assessments included hematology, clinical chemistry, coagulation testing, serological testing, pregnancy testing, cluster differentiation 4 (CD4). | SAS included all participants who received at least one dose of IP (i.e., FEIBA). Participants were counted more than once in the arm groups. Participants counted in Part 1 regular volume and in Part 1 reduced volume were the same. | Posted | Count of Participants | Participants | No | From first dose of study drug up to 7 days after the end of infusion (up to Day 41) |
|
|
|
| 0 |
| 33 |
| 3 |
| 33 |
| 2 |
| 33 |
| EG001 | Part 1:FEIBA 85±15 U/kg 50% Reduced Volume at 2 U/kg/Min Rate | Participants were randomized to receive 3 infusions of FEIBA 85 ± 15 U/kg, IV reconstituted in 50% reduced volume SWFI, at the standard rate of 2 U/kg/min, every 48 hours (Participants in Sequence A: infusions 4, 5, and 6 and Participants in Sequence B: infusions 1, 2 and 3). | 0 | 30 | 1 | 30 | 5 | 30 |
| EG002 | Part 2:FEIBA 85±15 U/kg 50% Reduced Volume at 4 U/kg/Min Rate | Participants who completed Part 1 of the study received up to 3 infusions of FEIBA 85 ± 15 U/kg IV reconstituted in 50% reduced volume SWFI at an increased rate of 4 U/kg/min, every 48 hours (infusions 7, 8, and 9). | 0 | 30 | 0 | 30 | 0 | 30 |
| EG003 | Part 2:FEIBA 85±15 U/kg 50% Reduced Volume at 10 U/kg/Min Rate | Participants who completed Part 1 of the study and received up to 3 infusions (infusions 7, 8, and 9) at the rate of 4 U/kg/min in Part 2 received up to 3 infusions (10, 11, and 12) of FEIBA 85 ± 15 U/kg IV reconstituted in 50% reduced volume SWFI at an increased infusion rate of 10 U/kg/min, every 48 hours. | 0 | 28 | 0 | 28 | 2 | 28 |
| Epilepsy | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 24.1 | Systematic Assessment |
|
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |